Alkamin and process of producing same.



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ALEX IB. DAVIS, OF INDIANAPOLIS, INDIANA, ASSI GNOR TO THE ELI LILLY AND COMPANY, OF INDIANAPOLIS, INDIANA, A CORPORATION OF INDIANA.

ALKAMIN AND PROCESS OF PRODUCING SAME.

No Drawing.

To all w/mm it may concern:

. Be it known that I, ALEX B. DAVIS, a citizen of the United States, residing at Indianapolis, Marion county, and State of Indiana, have invented and discovered certain new and useful Improvements in Alkamins and Processes of Producing Same, of which the following is a specification.

The invention relates to new alkamins derived "from halogen tertiary alcohols obtained by reacting upon new halogen ketones with alkyl, aryl or aralkyl magnesium haloids. Magnesium haloids of these groups are known as Grignard reagents.

More especially it relates to alkamins derived from halogen tertiary alcohols made by reacting upon epichlorhydrin with alkyl, aryl or aralkyl magnesium haloids, oxidizing the resulting carbinols and acting upon the thus obtained ketones with alkyl, aryl or aralkyl magnesium haloids.

The general process is as follows:

Step N 0. 1.Alkyl magnesium haloids of the general formula XMgZ in which X is any alkyl, aryl or aralkylgroup and Z any halogen, are allowed to react under the usual conditions of a Barbier Grignard reaction, with epichlorhydrin of the formula 0 err perpetual.

The reaction product upon decomposition with acids yields carbinols of the formula in which X is any alkyl, aryl or aralkyl group. 1

Step 1V0. 2.The carbinols thus obtained, upon oxidation yield ketones of the formula in which X is any alkyl, aryl or aralkyl group.

Specification of Letters Patent.

Patented Aug. 17, 1915.

Application filed May 23, 1914. Serial No. 840,576.

produce compounds, which when decomposed with acids yield halogen tertiary alcohols of the formula in which X and Y are alkyl,.aryl or aralkyl and A and B are alkyl and hydrogen. The esters of these substituted amino alcohols are valuable local anesthetics.

The following is a detailed description of the preparation of amino alcohol of this series according to the above described process:

Step N0. 1.In a flask provided with a reflux condenser there are placed 240 'grams of magnesium metal in any suitable form, a quantity of absolute ether is added and then 1370 grams of iso-butyl-bromid are gradually run in. The magnesium dissolves to form the compound C H H: CHz-CH c;: cH3-cm which is a combination of iso-butyl-magne'sium-bromid and ether. \Vhen all the magnesium has dissolved there are run into poured upon a mass of cracked ice and acidified with dilute sulfuric acid yields an ethereal solution of the desired carbinol. The ether layer rising to the top is separated, the ether distilled and the residue fractionated,

that fraction boiling between 1846 C. and

192 C. is saved and consists almost entirely formula of chlor-methyl-iso-amyl-carbi1fol of the" Step N 0. 2.1200 grams of the above de-' scribed carbinol are placed in a large flask. 800 grams of finely powdered potassium dichromate are added and the flask packed in ice. 1200 grams of sulfuric acid diluted with 1500 c. c. of water are then gradually added over a period of four hours with occasional shaking. When all the acid is added the flask is heated up gradually on the water bath for one hour and the mixture is then distilled with steam. The distillate is extracted with ether as many times as necessary, the ether extracts united, the ether distilled, and the residue fractionated the fraction boiling between 182 and 190 C. being saved. It consists mainly of chlor-methyliso-amyl ketone of the formula an t i 3 J a CH/ on, on, on, 01 Step N0. 3.In a flask provided with a reflux condenser there is placed a quantity of absolute ether and 156 grams of metallic magnesium in any suitable form. 700 grams of ethyl bromid are gradually run in and the magnesium dissolves to produce a compound of ether and ethyl magnesium bromid of the formula or: CH -M -Br o 3 cm-cn/ 800 grams of chlor-methyl-iso-amyl-ketone described in step No. 2, diluted are now run 1n. reaction takes place and the resulting mass is poured on to cracked ice, acidified with dilute sulfuric acid, the ether layer which rises to the top separated, the ether distilled and the residue fractioned in vacuum when the fraction boiling at 135 to 140 C. under about 80 m. m. is saved and consists of chlor-methyl-ethyl-iso-amyl-carbinol of the formula H b-cm-cm-t-om-ci united, the ether distilled and the residue fractioned in vacuum, that part boiling between 132 and 138 under about 80 m. m. being saved. It consits of dimethyl-aminomethyl-ethyl-iso-amyl-carbinol of the formula Esters of this compound are valuable local anesthetics.

What I claim is 1. In the process of producing alkamins the esters of which are local anesthetics, the

steps of reacting upon epichlorhydrin with 7 resulting secondary alcohols to produce ketones, reacting upon these ketones with organic megnesium haloids and condensing the resulting halogen tertiary alcohols with substituted amins to produce substituted tertiary amino alcohols.

3. The process of producing dimethyl; amino-methyl-ethyl-iso-amylcarbinol of the formula by reacting upon epichlorhydrin with isobutyl magnesium bromid, thus producing chlor methyl iso amyl carbinol, oxidizing this to chlor-methyl-iso-amyl ketone, reacting upon this ketone with ethyl magnesium bromid and condensing the resulting chlormethyl-ethyl-iso-amyl-carbinol with d1- methyl-amin, all as above described.

4. The alkamin of the probable formula In witness whereof, I have hereunto set my hand and seal at Indianapolis, Indiana, this sixth day of May, A. D. nineteen hundred and fourteen.

ALEX B. DAVIS. [1,. s.]

Witnesses:

E. G. EBERHARDT, ARTHUR L. WALTERS. 

